Evolution of research funding for neglected tropical diseases in Brazil, 2004–2020

Neglected tropical diseases are a global public health problem. Although Brazil is largely responsible for their occurrence in Latin America, research funding on the subject does not meet the population’s health needs. The present study analyzed the evolution of research funding for neglected tropical diseases by the Ministry of Health and its partners in Brazil, from 2004 to 2020. This is a retrospective study of data from investigations registered on Health Research (Pesquisa Saúde in Portuguese), a public repository for research funded by the Ministry of Health’s Department of Science and Technology. The temporal trend of funding and the influence of federal government changes on funding were analyzed using Prais-Winster generalized linear regression. From 2004 to 2020, 1,158 studies were financed (purchasing power parity (PPP$) 230.9 million), with most funding aimed at biomedical research (81.6%) and topics involving dengue, leishmaniasis and tuberculosis (60.2%). Funding was stationary (annual percent change of -5.7%; 95%CI -54.0 to 45.0) and influenced by changes to the federal government. Research funding was lacking for chikungunya, Chagas disease, schistosomiasis, malaria and taeniasis/cysticercosis, diseases with a high prevalence, burden or mortality rates in Brazil. Although the Ministry of Health had several budgetary partners, it was the main funder, with 69.8% of investments. The study revealed that research funding for neglected tropical diseases has stagnated over the years and that diseases with a high prevalence, burden and mortality rate receive little funding. These findings demonstrate the need to strengthen the health research system by providing sustainable funding for research on neglected tropical diseases that is consistent with the population’s health needs.

Comment 3: "They clearly explain the somewhat confuse Brazilian governmental system of research funding. However, my concern is that the international reader may remain still confused -anyhow, one cannot blame authors for that." Our response: Thank you for your comment. Indeed, the government funding system for research in Brazil is complex and can be difficult for international readers to understand. With this in mind, we have added Figure 1 to the Methods section to illustrate the public research funding process in Brazil and the governance system of the Ministry of Health's Department of Science and Technology, the focus of our manuscript. We have also changed the wording of the context of the study (line 107 to 142) in the methods section to help readers more clearly understand the research funding system in Brazil, as follows: In Brazil, the National Science, Technology and Health Innovation System includes state and federal agencies and institutions that finance, monitor and evaluate research either individually or collectively (Fig 1A) 19 . In the present study, we analyzed funding for NTD research from the Ministry of Health's Department of Science and Technology (MoH/DECIT).
In the federal sphere, within the Ministry of Health, DECIT is responsible for implementing National Policy on Science, Technology and Innovation in Health and coordinating health R&D via intersectoral partnerships for funding health research, particularly with: i) other Ministry of Health departments; ii) the Oswaldo Cruz Foundation (FIOCRUZ)affiliated with the Ministry of Health and one of the main public institutions that conducts health research in Brazil and produces drugs and biopharmaceuticals for the SUS; iii) the Ministry of Science, Technology and Innovations (MCTI)responsible for formulating and implementing National Policy on Science and Technology; iv) the Coordination for the Improvement of Higher Education Personnel (CAPES)affiliated with the Ministry of Education (MEC) and aimed at supporting professors and researchers via research grants and scholarships; v) national funding agencies (such as the National Council for Scientific and Technological Development -CNPq, a funding agency affiliated with the MCTI that funds scientific and technological research and innovation and helps train qualified human resources for research), as well as state (Research Support Foundations -FAPs, public institutions that finance scientific research in Brazilian states) and international funding agencies 15,16,[20][21][22]  Hiring: aimed at addressing the strategic demands of the Ministry of Health or emergency situations in public health, whereby researchers are hired directly without going through a public selection process.
In order to establish research funding priorities in public calls for tender or direct hiring, DECIT uses the National Agenda of Health Research Priorities as a guide, which is based on SUS principles and the national and regional health needs of Brazilians 26 . Appraisal seminars are held to monitor and assess research supported by DECIT ( Fig 1B).  Comment 5: "They also discuss this imbalance in terms of priority of funding and mortality/burden -that is, they complain that chikungunya, Chagas disease, malarial schistosomiasis and taeniasis/cysticercosis, which stand out in terms of prevalence and burden in Brazil, have received little research funding. However, an explanation for this may be the lack of submission of projects in these areas.

Our response:
We agree with your comment and have therefore included the following text in the

Discussion section (line 420-430):
It is believed that the small number of chikungunya studies funded is due to the date on which the disease was introduced in the country, since the first autochthonous cases were reported in 2014 46 . For taeniasis/cysticercosis, the lack of consolidated public policies to tackle the disease may have resulted in its being "forgotten" in research in the field.
For other diseases, the dearth of research may be related to the introduction of other topics defined as priorities in public calls for tenders for study selection, prompting research groups to focus on topics with available funding. Additionally, the occurrence of malaria, for example, which is concentrated in the Brazilian Amazon Forest in Northern and Midwestern states 47 , has made the disease a priority for these regions, meaning that often only researchers from these areas choose to study the topic.  The estimated coefficients were used to calculate trends via the Annual Percent Change (APC) parameter and respective 95% confidence intervals (CI), calculated based on the following formula: = [−1 + 10 1 100; 95% = [−1 + 10 1 ] 100; 1 + 10 1 max] 100 A positive APC indicates an increasing trend for the time series analyzed, a negative value a decreasing trend, and no statistically significant difference is classified as stationary 29 .

Results
"See the suggestions for the analysis." Our response: The suggestion has been accepted and temporal trend analysis redone.

Conclusions
"Some parts of the conclusion do not depend on the results of this study. Should be based on the evolution analysis." Our response: Thank you for your comment. We have restructured the conclusion of the manuscript to comply with the points raised by the reviewer. The complete response to this question can be found in Reviewer 2, comment 7.

Editorial and Data Presentation Modifications?
It is important to correct the analysis, this way the results and discussion would be fitted. that changes in management influenced funding during the study period (p value < 0.05) (Fig 2B).

Discussion:
Line 355 to 356: Although public funding for research on these diseases showed a stationary trend during this period, changes in the Brazilian federal government influenced the amount invested.

Line 385 to 392:
In addition to budget cuts, management changes in the Brazilian federal government affected investment in NTD research. It is important to underscore that although the same political party retained control of the federal government from 2004 to 2016, funding for NTD research fluctuated. This suggests that even with the same political party in power, changes occur that alter the direction of decision making on policies involving funding research with public resources.
Governments play a key role in implementing policies to address NTDs on a national level, including establishing priorities that guide health research funding 2,36 . The study revealed that research funding for neglected tropical diseases has stagnated over the years and that diseases with a high prevalence, burden and mortality rate receive little funding.

Summary and General Comments
These findings demonstrate the need to strengthen the health research system by providing sustainable funding for research on neglected tropical diseases that is consistent with the population's health needs.  It was concluded that while funding for NTD research remained stable, changes in the federal government influenced the amount invested during the time period studied. The lack of increased funding for NTD research may imply a decline in scientific production and the search for new knowledge that offers solutions to control these diseases.
Dengue, leishmaniasis and tuberculosis were the most studied diseases and received more funding, indicating that they are priorities for the federal government and researchers. On the other hand, few resources were available for studies on chikungunya, Chagas disease, schistosomiasis, malaria and taeniasis/cysticercosis, diseases with a high prevalence, burden or mortality rate in Brazil, which suggests that research funding does not reflect the epidemiological importance of these diseases in the country.
The most funding was allocated to biomedical research. Continued funding for biomedical research is important in obtaining answers to persistent problems involving NTDs; however, this finding demonstrates the need to expand the scope of funding to include other types of research, such as epidemiological studies, in healthcare services and clinics in order to assess the effectiveness of the surveillance strategies, treatments and diagnostics adopted and seek new sustainable solutions.
The Ministry of Health played a leading role in funding NTD research, but also collaborated with several budgetary partners, particularly FAPs. These intersectoral partnerships can contribute to maximizing the capture and use of financial resources.
Finally, the results of this study contribute to subsidizing assessments of governance structure in health research, which must be coherent and based on health needs in order to increase the capacity of health systems, services and policies and improve funding in a scenario of finite and limited resources.